Ebola and the immune system

I’ve often wished the immune system had a different name. One that sounded a lot more grand and complicated. It slips easily off the tongue and gulls people into thinking that it’s no more complicated than their central heating system. And that the equivalent of a tweak of the thermostat (in the form of a pill or a foot massage) can give “it” a quick boost. When researching my book I realised that it’s a system of a very different kind – more like, say, the complexity of a city like London with its workers, businesses, buildings and transport networks.

There are two main divisions to the immune system. The emergency “innate” division kicks in the minute you have a wound. On a much slower timescale the “adaptive” division learns about all the bacteria, viruses and proteins in your environment – which to ignore and which to attack with antibodies the next time they crop up. There are many different types of immune cell (“white blood cells”) and new sub-types are discovered regularly. They produce a vast array of complex proteins called cytokines that also play a role in attacking pathogens. Part of what we mean by “immune system” is this interacting mass of cells and proteins that flow through blood and tissues during health and illness. But there is more. The permanent structures of the immune system are the bone marrow, which is the production unit for replacement immune cells, and the lymphatic system that monitors threats throughout the body.

As in cities, balance is important. You don’t need a rail system that varies its timetable unpredictably. Neither do you need an immune system that is over- or under-active. Everything has to be modulated to keep things running smoothly so as to prevent not only infection but also self-damage. Diseases associated with an over-active immune system include all the auto-immune diseases, allergies and inflammatory conditions. Toxic shock, sepsis and the cytokine storm (which can occur in pandemic flu) are more sudden and much more deadly over-reactions.

Some illnesses are not just attacked by the immune system – they directly infect immune cells and interact with them in complex ways. It’s well known that the HIV retro-virus directly attacks immune cells, using them as a base and slowly undermining their work. TB, caused by a bacterium, also infects immune cells – the ones that normally engulf and destroy bacteria entering the lungs. Ebola too infects immune cells, and progresses far more swiftly than HIV or TB. It does so by using infected immune cells to spread the virus throughout the body. Ebola is also able to damp down aspects of the immune function. But that is not all. The high fever and inflammation of the later stages of the disease are part of a massive immune over-reaction that contributes to death. 

There are various scientific initiatives attempting to tackle this unusual virus but the solutions are not simple.

There are some anti-viral drugs undergoing accelerated trials but it would be surprising if they make a significant impact. The might of the pharmaceutical industry has yet to produce a range of wonder-working anti-virals for other diseases. Anti-retrovirals, used for HIV, are probably the biggest success, despite all their limitations. Vaccine development is a long and difficult road and vaccines in current development are a while away from any prospect of a  mass roll-out. The experimental biological treatment ZMapp is a product of immunological research. It’s a combination of artificially produced antibodies that lock on to specific targets on the Ebola virus, disabling it. It is to be hoped that ZMapp works, and that one day it can be produced in large enough quantities to be useful in bringing outbreaks under control. However production methods are complex involving a lot of careful work by technicians and the growth of cloned cells in laboratory conditions. This process is not at all like the factory production line that produces conventional chemical drugs. My feeling is that science is very unlikely to come up with any quick answers, with mass impact, in the next few months.

In the meantime though, simple nursing measures like infection control and putting up a drip can save lives. As Christmas looms we are asked to contribute to a wide range of charities but this year many of us will perhaps consider that paying for some nursing supplies for Ebola stricken areas is the most urgent call on our generosity.

http://www.bbc.co.uk/news/health-30217573

A New Role for Vitamin D ?

Everyone seems convinced that vitamin C has wonderful preventative and curative powers for viral illnesses like colds and 'flu despite the fact that there is very little evidence to support the belief. Evidence is starting to build though, that vitamin D might be much more significant in the maintenance of health.

There are two main ways to top up your vitamin D supplies. One is to expose you skin to sunlight and the other is to eat animal fats - in particular oily fish.  

It has been long been recognised as the substance that prevents rickets - a deficiency disease in babies and young children in which bones are inadequately calcified. The leg bones bend under the child's weight, the skull can be as thin as a ping-pong ball and the whole skeleton is deformed.

We now know that there are receptors for vitamin D on the surface of cells all over the body, including immune cells and not just in bone cells. Receptors are like mail boxes - you don't have them, unless you are expecting some mail. There is particular research interest in the way this vitamin interacts with tuberculosis (TB).

TB is a bacterial disease that has evolved a unique relationship the immune system. Many people infected with the TB bacterium remain healthy. The immune system often manages to contain pockets of infection as harmless nodules so that the disease is “latent”. As long as the immune system can successfully maintain this state of siege the TB cannot spread and inflict further damage. It is well know that those with an HIV-damaged immune system are susceptible.

Before the advent of antibiotics, TB was very difficult to treat but sunshine therapy was one of the methods that seemed to be helpful in pushing the disease back into latency. There is a complex interplay between immune cells and TB bacteria and there is a strong suspicion that one of the things that helps the immune system to maintain its ability to contain the disease is to have an adequate supply of vitamin D in the body. Research recently published seems to show that giving patients supplements of vitamin D (alongside their antibiotics) significantly speeds recovery.

There are other clinical trials taking place into the links between vitamin D and a range of diseases. This is one of the most interesting lines of current research, in terms of things individuals might be able to do to support the function of their own immune systems.

A variety of TB that is resistant to all available drug treatments is no longer a spectre but a reality. Several cases have been identified in India. Once this starts spreading across the globe, and spread it inevitably will, TB will become an incurable killer as it was in the 19^th and early 20^th centuries. Anything we can discover that will help people resist this disease will be important to individual and public health.

Queen Mary, University of London. "High doses of vitamin D help tuberculosis patients recover more quickly." ScienceDaily, 3 Sep. 2012. Web. 24 Sep. 2012. http://www.sciencedaily.com/releases/2012/09/120903154008.htm

Stem Cell Transplants to Cure AIDS?

I am always concerned when the press run stories of cures. The science may well be interesting but I feel compassion for those who have hopes raised.

There was much publicity recently about the man who was "cured of HIV" by a stem cell transplant. He was unfortunate enough to have leukaemia. And he was HIV positive. In the process of treating his leukaemia in 2007, with a procedure known as a stem cell transplant, it appears that the AIDS virus was cleared from his immune system and he remains healthy. It is possible though that HIV still lurks in his brain, beyond the reach of his immune cells.

So does this news offer hope for those who have to take a daily cocktail of antivirals to keep their HIV infection in check?

The stem cells that make up the red bone marrow produce the full range of "white blood cells" that, in turn, make up the immune system. Leukaemia is a disease of the bone marrow - one type of stem cell turns cancerous and the mix of immune cells is thrown wildly off balance, with fatal consequences. Stem cell transplants have superceded "bone marrow transplants". These days the stem cells can be harvested from the donor's blood using a process similar to a single session of dialysis.

If normal chemotherapy fails to cure a case of leukaemia, the only solution is to use stronger drugs to kill off the bone marrow. Then the patient is given a transplant of healthy stem cells from a donor. This rebuilds the immune system with cells that are genetically matched to the donor.

There are many risks and difficulties. While waiting for the transplant to start working, the patient's immune system dwindles to almost nothing for a few weeks, leaving them highly vulnerable to infection. Any pre-existing infections would run riot - so that probably excludes anyone suffering from AIDS. The other problem is finding a suitable donor. We have all heard of people who need a bone marrow transplant but cannot find a suitably matched donor. The problem is the huge variety of possible tissue types. The tissue types of patient and donor need to be very similar if they transplant is to work. Rejection can bring life-threatening complications. So a stem cell transplant is a risky, expensive, treatment-of-last-resort, that is only used in a minority of cases of leukaemia.

 In this remarkable case the patient was able to receive a transplant from another unusual person - someone who had a natural immunity to HIV. These people are extremely rare. So it was not necessarily the transplant that cleared the virus - it might have been the particular genetic makeup of the donated cells.

 So to use this as a treatment for HIV you would need a reasonably healthy patient who has not succumbed to any AIDS-related infections and a matched donor, with a very special, very rare immune system.  

This was not an experiment. An imaginative doctor identifying an opportunity and tried something new. It could well turn out to be a one-off case, thought provoking for scientists, but for the time being (sadly) a million miles away from being a realistic prospect as a treatment for HIV. A cure for HIV may someday be found, but it will result from painstaking research and not from stem cell transplants as we know them today.